In mouse mammary epithelium, genetic, hormonal, and oncogenic factors interact. The purpose of this project is to understand the regulatory role of the nuclear envelope during hormone-dependent differentiation. We will study the nuclear envelope proteins of mouse mammary epithelial cells and their regulatory significance in cell growth, hormone-directed differentiation, and mammary tumor virus transformation. Following preliminary studies with established cell lines of cultured mammalian cells, we plan to isolate, identify and describe the nuclear envelope of mouse mammary epithelium in vivo from normal mature mice at successive states of hormone-induced differentiation. A comparative examination of tumor-bearing mice and of tumor tissue should enable us to comprehend better the relation of differentiation- associated changes in the nuclear membrane of tumor susceptibility, induction, and growth. Our second objective is to set up a cell culture system in a controlled environment where the interactions of these factors can be studied by radioisotope tracer techniques. In primary monolayer cultures we can produce the various differentiated states by augmenting the nutritive environment with hormones. The in vivo and in vitro enzymological, biochemical, electron microscopic, and electrophoretic characterization of nuclear envelope free normal and tumor-bearing mice will serve as a background for our long-range goal to study (1) transport of macromolecules through membranes of isolated nuclei, (2) biochemical and functional changes in nuclear membrane produced by hormones, (3) cyclic assembly and disassembly of the nuclear envelope during mitosis, (4) the regulatory function of the nuclear membrane in DNA biosynthesis, and (5) the role of the nuclear envelope in the expression of certain oncogenic viruses (other than mammary tumor virus) with which it directly interacts.